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Ethnic Differences of two Non-synonymous Single Nucleotide Polymorphisms in CDA Gene
Sugiyama, E.,Lee, S.J.,Lee, S.S.,Kim, W.Y.,Kim, S.R.,Tohkin, M.,Hasegawa, R.,Okuda, H.,Kawamoto, M.,Kamatani, N.,Sawada, J.i.,Kaniwa, N.,Saito, Y.,Shin, J.G. 日本藥物動態學會 2009 DRUG METABOLISM AND PHARMACOKINETICS Vol.24 No.6
Cytidine deaminase, encoded by the CDA gene, catalyzes anti-cancer drugs gemcitabine and ara-C into their respective inactive metabolites. In CDA, two functionally significant non-synonymous polymorphisms, 79A>C (Lys27Gln) and 208G>A (Ala70Thr), have been found and their minor allele frequencies (MAFs) were reported in Japanese and Chinese patients and a relatively small numbers of healthy volunteers in Caucasians and Africans. In this study, we determined the MAFs of both polymorphisms in 200 healthy volunteers of Koreans, along with 206 Japanese, 200 Chinese-Americans, 150 Caucasian-Americans and 150 African-Americans to reveal ethnic differences. MAFs of 79A>C (Lys27Gln) were 0.153 in Koreans and 0.327 in Caucasian-Americans, 0.204 in Japanese, 0.155 in Chinese-Americans and 0.087 in African-Americans. MAFs of 208G>A (Ala70Thr) were 0.005 in Koreans and 0.022 in Japanese and the minor allele was not detected in Chinese-Americans, Caucasian-Americans or African-Americans. Thus possibly, MAF of 208G>A in Japanese is likely to be somewhat higher than in Koreans and Chinese-Americans. These data would provide fundamental and useful information for pharmacogenetic studies on cytidine deaminase-catalyzing drugs.
Taniguchi, Junichi,Pandian, Ganesh N.,Hidaka, Takuya,Hashiya, Kaori,Bando, Toshikazu,Kim, Kyeong Kyu,Sugiyama, Hiroshi Oxford University Press 2017 Nucleic acids research Vol.45 No.16
<P><B>Abstract</B></P><P>Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole–imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing knowledge about key transcriptional changes during the induction of cardiomyocyte, we developed a DNA-binding inhibitor termed <B>PIP-S2</B>, targeting the 5′-CTTTGTT-3′ and demonstrated that inhibition of SOX2–DNA interaction by <B>PIP-S2</B> triggers the mesoderm induction in hiPSCs. Genome-wide gene expression analyses revealed that <B>PIP-S2</B> induced mesoderm by targeted alterations in SOX2-associated gene regulatory networks. Also, employment of <B>PIP-S2</B> along with a Wnt/β-catenin inhibitor successfully generated spontaneously contracting cardiomyocytes, validating our concept that DNA-binding inhibitors could drive the directed differentiation of hiPSCs. Because PIPs can be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to target and regulate key transcription factors specifically associated with desired cell types.</P>
H. Yoda,Y. Ohsawa,Y. Kato,N. Shimomura,M. Shimizu,K. Koi,S. Shirotori,T. Inokuchi,H. Sugiyama,S. Oikawa,B. Altansargai,M. Ishikawa,A. Kurobe 한국자기학회 2019 Journal of Magnetics Vol.24 No.1
We designed a voltage-control spintronics memory unit-cell, VoCSM, with high write-efficiency to prove a potential to reduce writing energy per bit. By optimizing a self-aligned structure, the cell has the critical switching current (Icsw) smaller than 50 μA at 20 nsec. for designed MTJ size of about 50 × 150 ㎚². The value is much smaller than that for mature STT-MRAM with the similar dimension. VoCSM also was proved to have unlimited endurance. Finally, with an empirical equation of Icsw further reduction of Icsw is estimated to clarify that VoCSM has a potential to reduce Icsw down to several μA.
Ueta, M.,Sawai, H.,Sotozono, C.,Hitomi, Y.,Kaniwa, N.,Kim, M.K.,Seo, K.Y.,Yoon, K.C.,Joo, C.K.,Kannabiran, C.,Wakamatsu, T.H.,Sangwan, V.,Rathi, V.,Basu, S.,Ozeki, T.,Mushiroda, T.,Sugiyama, E.,Maekaw Mosby 2015 The Journal of allergy and clinical immunology Vol.135 No.6
Background: Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface, oral cavity, and genitals. These reactions are very rare but are often associated with inciting drugs, infectious agents, or both. Objective: We sought to identify susceptibility loci for cold medicine-related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement (SMI). Methods: A genome-wide association study was performed in 808 Japanese subjects (117 patients with CM-SJS/TEN with SMI and 691 healthy control subjects), and subsequent replication studies were performed in 204 other Japanese subjects (16 cases and 188 control subjects), 117 Korean subjects (27 cases and 90 control subjects), 76 Indian subjects (20 cases and 56 control subjects), and 174 Brazilian subjects (39 cases and 135 control subjects). Results: In addition to the most significant susceptibility region, HLA-A, we identified IKZF1, which encodes Ikaros, as a novel susceptibility gene (meta-analysis, rs4917014 [G vs T]; odds ratio, 0.5; P = 8.5 x 10<SUP>-11</SUP>). Furthermore, quantitative ratios of the IKZF1 alternative splicing isoforms Ik1 and Ik2 were significantly associated with rs4917014 genotypes. Conclusion: We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects and showed that the Ik2/Ik1 ratio might be influenced by IKZF1 single nucleotide polymorphisms, which were significantly associated with susceptibility to CM-SJS/TEN with SMI.
M. Shimizu,Y. Ohsawa,H. Yoda,S. Shirotori,B. Altansargai,N. Shimomura,Y. Kato,S. Oikawa,H. Sugiyama,T. Inokuchi,K. Koi,M. Ishikawa,K. Ikegami,A. Kurobe Korean Magnetics Society 2018 Journal of Magnetics Vol.23 No.4
A voltage-control spintronics memory (VoCSM) which has a potential of low energy consumption uses the spin-Hall effect (SHE) and the voltage-controlled magnetic anisotropy (VCMA) effect for its write operation. In this work, the relationship between the critical switching current (Icsw) and the SHE electrode thickness (tN) is investigated in the range of 5 nm < tN < 8 nm. In the fabrication process, we develop highly-selective patterning process to stop MTJ etching precisely on the surface of the SHE electrode. Using the technique, Icsw is reduced by half as tN is varied from 8 nm to 5 nm, and Icsw of 112 mA at 20 ns write current pulse is obtained for MTJ size of 50 × 150 nm2 on Ta(2 nm)/TaB (3 nm) electrode. The results indicate that the decrease in the SHE electrode thickness is a promised method to reduce Icsw, which leads VoCSM to a low-energy-consumption device.